Patients treated with the
immunosuppressant and anticancer drugs
6-thioguanine,
azathioprine, or
mercaptopurine can metabolize and incorporate them in
DNA as
6-thioguanosine. The skin of these patients is sensitive to UVA radiation, and long-term treatment can result in extremely high incidence of sunlight-induced
skin cancer. In this contribution the photophysics of
6-thioguanosine have been studied in aqueous
buffer solution and in
acetonitrile after excitation with UVA light to provide mechanistic insights about the origin of its
phototoxicity. It is shown that most of the initial excited-state population in the S(2)(ππ*, L(a)) state decays by ultrafast intersystem crossing to the triplet manifold. A triplet quantum yield of 0.8 ± 0.2 is determined in aqueous
buffer solution. A minor fraction of the S(2) population bifurcates on an ultrafast time scale to populate the S(1)(n(S)π*) state, which decays back to the ground state in
tens of picoseconds. Quantum-chemical calculations that include
solvent effects support the experimental results. The high triplet yield of
6-thioguanosine, which we argue can result in
photosensitization of molecular
oxygen and photooxidative DNA damage, is proposed to explain the high
phototoxicity exhibited by these
pro-drugs in patients upon sunlight exposure. Finally, the experimental and computational results for
6-thioguanosine are compared with those reported for the
DNA/
RNA guanine monomers.